tbuckley/cabot-search huggingface dataset:
Abstract 683: Vaccination against androgen receptor splice variant induces anti-tumor adaptive immune responses
Authors: Robert D. Marek, Junping Wei, Tao Wang, Xiao-Yi Yang, Gangjun Lei, Zachary C. Hartman
Journal: Cancer Research (2023)

Abstract Background: Androgen receptor (AR) signaling has been the central target for standard-of-care prostate cancer therapies, although de novo resistance to these therapies occurs in many metastatic prostate cancer patients within 2-3 years. Resistance to AR targeting agents most often develops through overexpression of AR and expression of truncated, constitutively active RNA splice variants of AR. While clinical use of PD-1/PD-L1 immune checkpoint blockade has failed to demonstrate clinical success in treating resistance prostate cancers, the slower progression of prostate cancer provides an opportunity for immune targeted interventions. Cancer specific vaccines have the potential to enable and enhance tumor specific immune responses by stimulating and directing T cell immunity to important oncologic targets. We hypothesized that a cancer vaccine designed to induce a T cell response against cells expressing high levels of AR would result in an anti-tumor effect and potentially prevent or delay the development of therapeutic resistance. Methods: To evaluate AR and AR variants as potential immunological targets, we produced adenoviral vaccines against AR (Ad-AR) or AR splice variant 7 (Ad-AR-V7). We vaccinated naïve mice and examined AR and AR variant specific immunity in peptide restimulation. We further tested our vaccines in prophylactic and therapeutic regimens using multiple subcutaneous syngeneic tumor models (including prostate tumor lines, such as TrampC2) which were engineered to express AR or AR-V7. Results: Adenoviral vaccines targeting AR or AR-V7 produced robust T-cell responses against the N-terminal domain of AR. Notably, vaccination with both Ad-AR or Ad-AR-V7 induced significant anti-tumor immune responses, inducing complete tumor clearance against tumors expressing AR-V7 and allowing for long-term survival in the majority of vaccinated mice. Conclusions: These data demonstrate the potential of AR and AR splice variants as immunologic targets of prostate cancer vaccines, which elicit AR specific T cell immunity and produce anti-tumor responses in prostate cancers. Citation Format: Robert D. Marek, Junping Wei, Tao Wang, Xiao-Yi Yang, Gangjun Lei, Zachary C. Hartman. Vaccination against androgen receptor splice variant induces anti-tumor adaptive immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 683.
Abstract 4554: Head and neck cancer HuBiogel-embedded microtumor assay system for therapeutic efficacy testing of patient tumor specimens
Authors: Christopher D. Willey, Yedeh P. Ying, Anthony B. Morlandt, Hope M. Amm, Patricia H. Hicks, Joshua C. Anderson, Andee M. Beierle, Carissa M. Thomas, Jason M. Warram, Jingsong Chen, Jeffrey A. Thomas, Katie Banko, Raj K. Singh
Journal: Cancer Research (2023)

Abstract Head and neck (HN) cancer recurrence is common, and selecting effective salvage systemic therapy remains difficult, particularly for oral cavity cancers. Developing a rapid, robust and predictive therapeutic testing system could support clinical decision-making and improve patient outcomes. We developed a Patient Therapy Evaluation System (PTES) that employs a three-dimensional (3D) fully human microtumor drug testing assay using tissue specimens collected during surgery of HN cancers. Remnant fresh tumor tissue from patients is dissociated into single-cell suspension that is embedded using a novel HuBiogel-cell encapsulation technology (3D microtumors). This high-throughput assay platform allows morphologic, functional, and molecular evaluations in parallel by real-time imaging, cell proliferation, and biomarker protocols. Microtumor viability, growth profiles, and drug screening data are captured at multiple time points up to 14 days. Our initial cohort included 57 patient specimens (53 squamous cell carcinomas, 1 verrucous carcinoma, 1 osteosarcoma, 1 ameloblastoma, and 1 non-cancerous lichenoid mucositis). HuBiogel-embedded tumor cells formed numerous multicellular colonies exhibiting distinct organization and growth patterns in 14-day microtumor cultures. Interestingly, epithelial, stromal and stem-cell like populations were preserved in HN microtumor models based on marker expression. Treatment with single (cisplatin, 5FU, docetaxel) drugs and their combinations resulted in tumor inhibitory responses (IC50) evaluated by CellTiter-Glo assay, and residual surviving cells were also recorded by Calcein-AM staining of 3D Microtumors. While patient-derived HN microtumors were produced with high success rates, factors associated with lower microtumor yield included smaller tumor specimens and low viability after dissociation. In conclusion, our new all human microtumor assay models replicating phenotypic, functional, and molecular properties ex vivo provide a potential theranostic tool for rapidly predicting drug sensitivity and improving treatment strategy for HN cancer patients. Citation Format: Christopher D. Willey, Yedeh P. Ying, Anthony B. Morlandt, Hope M. Amm, Patricia H. Hicks, Joshua C. Anderson, Andee M. Beierle, Carissa M. Thomas, Jason M. Warram, Jingsong Chen, Jeffrey A. Thomas, Katie Banko, Raj K. Singh. Head and neck cancer HuBiogel-embedded microtumor assay system for therapeutic efficacy testing of patient tumor specimens. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4554.
Abstract 4935: Cannabidiol and cannabis extract protect cells against platinum-based chemotherapy via cellular uptake
Authors: Tereza Buchtová, Lucie Beresova, Katarina Chroma, Martin Mistrik
Journal: Cancer Research (2023)

Abstract Cannabinoids including cannabidiol belong between constituents of cannabis sp. (marijuana plant). Purified or as a part of cannabis products, the compounds are frequently used by cancer patients to attenuate chemotherapy-induced side effects such as pain, nausea, and vomiting. The presence of cannabis products on the public market expands each year while the illegality status weakens in an increasing number of countries. U.S. Food and Drug Administration has approved several cannabis-based drugs for seizures induced by Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex, also for the lost appetite of AIDS patients, and chemotherapy-induced nausea and vomiting. Oncological patients are further and strongly motivated to take the drugs in combination with chemotherapy by numerous reports demonstrating the anticancer effects of cannabinoids. Nevertheless, here we present unsettling data that cannabis extract together with CBD negatively interferes with worldwide approved platinum-based drugs cisplatin, carboplatin, and oxaliplatin. The phenomenon is proven across three cellular models including primary cells. Even low concentrations of cannabidiol or cannabis extract reduced the toxicity of platinum-based drugs using long-term colony forming assay and/or short-term crystal violet assay. Increased resistance of cells was also accompanied by decreased cellular stress as evaluated by quantitative immunofluorescence microscopy and immunoblotting. Most importantly, concomitant cannabidiol and cisplatin exposure results in the decreased presence of cisplatin-modified DNA. Following the information, we determined platinum content in cells by ICP-MS. The experiment uncovered significantly decreased intracellular platinum content indicating an effect on cellular transport. Furthermore, the mechanism is translational independent as shown by the experiment with cycloheximide. This study offers crucial information that patients and physicians should take into account regarding possible interactions between platinum-based drugs and cannabis-based products. Furthermore, the study on the contradictory effects of cannabis products in cancer treatment may be motivated by this project. Citation Format: Tereza Buchtová, Lucie Beresova, Katarina Chroma, Martin Mistrik. Cannabidiol and cannabis extract protect cells against platinum-based chemotherapy via cellular uptake. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4935.
Abstract 6756: Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric cancer who previously treated with first-line nivolumab plus chemotherapy
Authors: Youngkyung Jeon, Sun Young Jeong, Jaeyeon Jang, Ye Ji Jung, Daeho Choi, Joohyun Hong, Seung Tae Kim, Won ki Kang, Jeeyun Lee
Journal: Cancer Research (2023)

Abstract Background: For human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (AGC), a combination of fluoropyrimidines and platinum agents was the standard first-line treatment. After the failure of the first-line therapy, ramucirumab plus paclitaxel was the standard second-line treatment. In the CheckMate 649 study, nivolumab plus chemotherapy has been considered a new standard first-line treatment in previously untreated AGC. However, the role of ramucirumab plus paclitaxel as 2nd line after the failure of nivolumab plus chemotherapy is not confirmed. Methods: We analyzed AGC patients with ramucirumab plus paclitaxel as second-line therapy, who failed the nivolumab plus chemotherapy (capecitabine plus oxaliplatin (XELOX) or 5-fluorouracil plus oxaliplatin (FOLFOX)) as frontline therapy at Samsung Medical Center, South Korea. Results: Under the routine clinical practice, 23 AGC patients, who progressed after first-line chemotherapy with nivolumab plus chemotherapy, were treated with ramucirumab plus paclitaxel between Dec 2021 to Sep 2022. The median age was 56 (range, 24-76), and 18 (78.3%) patients received nivolumab plus XELOX, while 5 (21.7%) patients received nivolumab plus FOLFOX. The overall response rate (ORR) to ramucirumab plus paclitaxel was 10.0% (2 of PR) and the disease control rate was 55.0%. At the median follow-up of 4.5 months, the median progression-free survival (PFS) from second-line ramucirumab plus paclitaxel commencement was 2.7 months (95% confidence interval (CI), 1.7-3.7); 6.9 months (95% CI, not calculated) in the first nivolumab plus chemotherapy responders(n=7), and 2.3 months (95% CI, 1.6-3.0) in non-responders(n=15) (p=0.232). At the time of data cutoff, 6 patients continued to receive ramucirumab plus paclitaxel and the median OS was 6.3 months (95% CI, 4.9-7.7). Conclusions: This analysis showed that ramucirumab plus paclitaxel as 2nd line therapy was not sufficient in AGC patients after the failure for nivolumab plus chemotherapy. The new innovative 2nd line therapy might be needed in AGC patients after nivolumab plus chemotherapy. Citation Format: Youngkyung Jeon, Sun Young Jeong, Jaeyeon Jang, Ye Ji Jung, Daeho Choi, Joohyun Hong, Seung Tae Kim, Won ki Kang, Jeeyun Lee. Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric cancer who previously treated with first-line nivolumab plus chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6756.
Abstract 728: Socio-economic and health disparity determinants of breast cancer prevalence in low-income counties in Alabama and Mississippi: An analysis of Deep South cancer epidemic
Authors: Ram Alagan
Journal: Cancer Research (2023)

Abstract Background: Studies underscore evidence that socioeconomic status (SES) is associated with breast cancer (BC)prevalence and especially poor SES is closely related to the cancer epidemic. Exploring the high and low SES status concerning BC prevalence is timely and noteworthy. Two impoverished Deep South states Alabama and Mississippi are the focus of this research. Alabama and Mississippi are well known for the historical and cultural landscape of Black Belt Counties (BBC), predominantly occupied by African American populations who were systematically undermined in many socioeconomic, healthcare, educational, and political aspects. Our investigation explores BC prevalence in the major ethnic groups (African American and White) in both southern states, mainly in the BBC. Hypothesis/Objectives: We hypothesized that SES is closely associated with BC prevalence. In particular, the poor status of SES severely influences BC patients' access to healthcare, healthy food, obesity, education, employment, transportation, prevention, and screening. Our study explores the impact of selected SES factors to understand BC prevalence in both states, particularly in impoverished BBC. Methods: We utilized Geospatial Technology (GT) to analyze the connection between BC prevalence and SES. This study incorporates county-level BC prevalence and association with SES, education, healthy food access, and health disparities. A robust data mining (U.S. Census, State Cancer Profile, Department of Health, American cancer society, National Cancer Institute, and published peer-reviewed journals) enabled us to explore the association between BC in the geospatial context. Integrating geospatial and non-spatial data on BC prevalence with SES will help predict and formulate BC prevention methods and promote health policy formulation and intervention in deep southern states. Conclusions: Alabama and Mississippi are the top states concerning the BC epidemic. The research employed SESand cancer prevalence using GT. Data shows a close relation between SES and cancer prevalence. The research strongly recommends the states adopt cancer awareness programs, and social and health equity policy planning. Citation Format: Ram Alagan. Socio-economic and health disparity determinants of breast cancer prevalence in low-income counties in Alabama and Mississippi: An analysis of Deep South cancer epidemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 728.
Abstract 675: Understanding SETDB1-mediated tumor immune evasion mechanism in endometrial cancer
Authors: Kiarash Salari, Matthew Wells, Eleanor R. Johnson, Tianyue Li, Jiaqing Hao, Bing Li, Shujie Yang
Journal: Cancer Research (2023)

Abstract SETDB1 is characterized as an important epigenetic regulator in many different cancers and involved in transcriptional silencing of many different processes and pathways. It is often overexpressed in many different cancers including colon, melanoma, breast and pancreatic cancers and its high expression is correlated with worse patient outcome. Often associated with repressing complexes such as HUSH and KAP1/KRAB, it has been shown to repress many different genes such as p53 and p21 through histone H3K9 methylation. In addition, it has been implicated in regulating transposable elements (TEs), primarily of the LTR types as well as SINEs and LINEs. Activation of TEs is key to induction of anti-viral response genes such as the type I interferon pathway and immune-stimulated genes (ISGs) which in turn promote innate immune response against the tumor. Here, we show that SETDB1 promotes tumor growth in endometrial cancer possibly through establishing an immune evasion from the innate immune system. Mice subcutaneously injected with SETDB1 depleted endometrial cancer cells show prolonged survival time and reduced tumorigenesis. In NSG mice, we demonstrate that subcutaneously injected endometrial cancer cell, ISHIKAWA, shows both increased penetration and recruitment of macrophages in the tumor when SETDB1 is knocked out. Our macrophage-cancer cells co-culture in-vitro assay suggests that macrophages induce greater killing in SETDB1-/- cells when stimulated into M1 phenotype more so than in WT cancer cells. Further, tumor IHC analysis shows greater proliferation capacity for control tumor relative to SETDB1-/- as evident by greater mitotic figures per unit area and Ki67 staining score. We further show that cytokines such as CCL5 and CXCL9 (previously reported for their positive correlation with T-cell infiltration in tumor) are significantly upregulated in SETDB1 knockout tumors relative to non-targeting control tumors (NT) as well as in cell lines. Endometrial cancer TCGA data show significant negative correlation between SETDB1 and markers of T-cell infiltration such as CD8A and IFNG as well as cytokines CCL5 and CXCL9. Overall, these findings show important implication of SETDB1 in macrophage recruitment and macrophage-mediated killing of cancer cells in addition to its role in promoting tumor cells proliferation. Citation Format: Kiarash Salari, Matthew Wells, Eleanor R. Johnson, Tianyue Li, Jiaqing Hao, Bing Li, Shujie Yang. Understanding SETDB1-mediated tumor immune evasion mechanism in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 675.
Abstract 6748: Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in resectable, locally advanced gastroesophageal junction and gastric carcinoma
Authors: Hongyan Yin, Qian Yao, Keren Jia, Dongfeng Niu, Xiaoyi Chong, Yanyan Li, Xujiao Feng, Yilin Li, Lin Shen, Yang Chen
Journal: Cancer Research (2023)

Abstract Background: Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Methods: 376 patients with GEJ or GC receiving NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to examine the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to elucidate the relationships between TRG combined with ypN status and prognosis. Results: We observed significant survival differences among the four groups (P &amp;lt; 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0 and TRG0-1N+ were not reached, whereas median DFS and OS of patients with TRG2-3N+ were 17.37 months (95%CI, 14.14 to 20.60 months) and 39.97 months (95%CI, 27.05 to 52.89 months). TRG combined with ypN status was an independent predictor for both DFS (P &amp;lt; 0.001) and OS (P &amp;lt; 0.001) in multivariate analysis. Additionally, TRG combined with ypN status was significantly associated with different NAT (P &amp;lt; 0.001). The TRG0N0 rate in patients accepting immunotherapy was 31.9%, which was the highest in all regimens. Conclusion: Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate. Citation Format: Hongyan Yin, Qian Yao, Keren Jia, Dongfeng Niu, Xiaoyi Chong, Yanyan Li, Xujiao Feng, Yilin Li, Lin Shen, Yang Chen. Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in resectable, locally advanced gastroesophageal junction and gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6748.
Abstract 4957: The targeting drug conjugate Tye1001 displayed its potent anti-tumor efficacy in lymphoma
Authors: Lichun Sun, Mengli Yang, Haihua Xiao, Yuan Tian, Natalya Vasilevich, Joseph Fuselier, David Coy
Journal: Cancer Research (2023)

Abstract Multiple drug-targeting strategies have been applied to drug development in order to reduce the toxic side effects of the traditional chemotherapy while enhancing its anti-tumor efficacy. Various peptides, proteins and antibodies are usually used to conjugate cytotoxic agents via acting as drug delivery vehicles. In our previous studies, we identified that peptides displayed their efficacious functions to deliver small molecules or oligo DNA to the target sites through ligand-receptor interactions and quick internalization. In our present study, we attempt to synthesize serial drug conjugates via coupling these compounds to peptide or protein vehicles. Tye1001, one of these conjugates, displayed similar potent anti-proliferation activities in lymphoma cells and many other cancer cells compared to the small molecule itself. In particular, this conjugate significantly enhanced its potent anti-tumor efficacy in xenografts. Meanwhile, this conjugate has much less toxic side effects. In our in vivo assays, the similar results were also observed in multiple other tumors such as gastric cancer and leukemia. Our findings provide a more potential druggable opportunity in the clinical applications of cancer patients and the treatment of different types of cancers. Citation Format: Lichun Sun, Mengli Yang, Haihua Xiao, Yuan Tian, Natalya Vasilevich, Joseph Fuselier, David Coy. The targeting drug conjugate Tye1001 displayed its potent anti-tumor efficacy in lymphoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4957.